RRC ID 22041
著者 Nakagawa-Yagi Y, Sato Y, Matsumoto E, Nakatsuka S, Sakaki T, Muramatsu Y, Hara T, Aigaki T.
タイトル Pharmacological modulation of histone demethylase activity by a small molecule isolated from subcritical water extracts of Sasa senanensis leaves prolongs the lifespan of Drosophila melanogaster.
ジャーナル BMC Complement Altern Med
Abstract BACKGROUND:Extracts of Sasa senanensis Rehder are used in traditional Japanese medicine; however, little is known about the underlying mechanisms of their potential health benefits.
METHODS:S. senanensis leaves were extracted with subcritical water. An active small-molecule was isolated using reversed-phase high-performance liquid chromatography (HPLC), and identified as 3,4-dihydroxybenzaldehyde (protocatechuic aldehyde or PA). The effects of PA on the activity of histone demethylase, the Drosophila melanogaster lifespan and gene expression in Drosophila S2 cells were investigated.
RESULTS:PA inhibited the activity of Jumonji domain-containing protein 2A (JMJD2A) histone demethylase in a dose-dependent manner with a half-maximal inhibitory concentration (IC50) of 11.6 μM. However, there was no effect on lysine-specific demethylase 1 (LSD1), histone deacetylase 1 (HDAC1) or HDAC8. PA significantly extended the lifespan of female, but not male, Drosophila. In Drosophila S2 cells, the eukaryotic translation initiation factor 4E binding protein (4E-BP) was up-regulated by PA exposure.
CONCLUSIONS:Our findings provide insight into the possible relationship between the pharmacological modulation of histone demethylation and lifespan extension by PA; they might also be important in the development of alternative therapies for age-related disorders.
巻・号 12
ページ 101
公開日 2012-7-18
DOI 10.1186/1472-6882-12-101
PII 1472-6882-12-101
解説 PMC3551771
PMID 22809229
PMC PMC3551771
MeSH Animals Benzaldehydes / chemistry Benzaldehydes / isolation & purification Benzaldehydes / pharmacology* Catechols / chemistry Catechols / isolation & purification Catechols / pharmacology* Drosophila melanogaster / drug effects* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism Enzyme Inhibitors / chemistry Enzyme Inhibitors / isolation & purification Enzyme Inhibitors / pharmacology* Female Gene Expression / drug effects Histone Demethylases / antagonists & inhibitors* Histone Demethylases / chemistry Humans Life Expectancy Male Models, Animal Models, Molecular Plant Extracts / chemistry Plant Extracts / isolation & purification Plant Extracts / pharmacology* Plant Leaves / chemistry Sasa / chemistry* Species Specificity
IF 2.833
引用数 5
WOS 分野 INTEGRATIVE & COMPLEMENTARY MEDICINE
リソース情報
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